The peroxynitrite ion (ONOO−) is a potent oxidant formed by the combination of nitric oxide (NO) and the superoxide anion (O2)—. NO has been shown to be generated by numerous cell types, such as macrophages, neutrophils, hepatocytes and endothelial cells. The direct combination of NO with O2 produces the peroxynitrite ion (ONOO−), which decomposes rapidly under physiological conditions to oxidizing intermediates. These oxidizing intermediates can damage biological targets.
Pathological consequences associated with damage to biological targets can include the oxidizing or nitrating of proteins, lipids and DNA. ONOO− crosses lipid membranes at a rate significantly faster than the rates of other known oxidants, indicating that this oxidant can travel distances of cellular dimensions. Thus, even in the presence of biological membranes, ONOO− can have free access to cellular interiors. ONOO− is also known to nitrate tyrosine residues in proteins, and to oxidize sulfhydryls, methionines and macromolecules such as, for example, metalloenzymes, DNA, and lipids.
In light of this reactivity, ONOO− has been implicated in a variety of diseases. These diseases include, e.g., neurodegenerative disorders such as Alzheimer's disease, amyotrophic lateral sclerosis, stroke, AIDS dementia and Huntington's disease; heart diseases such as atherosclerosis; chronic inflammation and autoimmune diseases such as arthritis, inflammatory bowel disease, and acute respiratory disease syndrome; cancer; ischemia-reperfusion injury; septic shock; and chronic rejection of renal grafts.